{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T21:59:24Z","timestamp":1775167164078,"version":"3.50.1"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T00:00:00Z","timestamp":1359072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2013,2]]},"abstract":"Summary<\/jats:title>Purpose<\/jats:title>Pyridoxine\u2010dependent epilepsy seizure (PDE<\/jats:styled-content>;OMIM<\/jats:styled-content>266100) is a disorder associated with severe seizures that can be controlled pharmacologically with pyridoxine. In the majority of patients withPDE<\/jats:styled-content>, the disorder is caused by the deficient activity of the enzyme \u03b1\u2010aminoadipic semialdehyde dehydrogenase (antiquitin protein), which is encoded by theALDH7A1<\/jats:italic><\/jats:styled-content>gene. The aim of this work was the clinical, biochemical, and genetic analysis of 12 unrelated patients, mostly fromS<\/jats:styled-content>pain, in an attempt to provide further valuable data regarding the wide clinical, biochemical, and genetic spectrum of the disease.<\/jats:p><\/jats:sec>Methods<\/jats:title>The disease was confirmed based on the presence of \u03b1\u2010aminoadipic semialdehyde (\u03b1\u2010AASA<\/jats:styled-content>) in urine measured by liquid chromatography tandem mass spectrometry (LC\u2010MS\/MS) and pipecolic acid (PA<\/jats:styled-content>) in plasma and\/or cerebrospinal fluid (CSF<\/jats:styled-content>) measured by high performance liquid chromatography (HPLC<\/jats:styled-content>)\/MS<\/jats:styled-content>\/MS<\/jats:styled-content>and by sequencing analysis of messenger RNA (mRNA<\/jats:styled-content>) and genomicDNA<\/jats:styled-content>ofALDH7A1<\/jats:italic><\/jats:styled-content>.<\/jats:p><\/jats:sec>Key Findings<\/jats:title>Most of the patients had seizures in the neonatal period, but they responded to vitaminB<\/jats:styled-content>6 administration. Three patients developed late\u2010onset seizures, and most patients showed mild\u2010to\u2010moderate postnatal developmental delay. All patients had elevatedPA<\/jats:styled-content>and \u03b1\u2010AASA<\/jats:styled-content>levels, even those who had undergone pyridoxine treatment for several years. The clinical spectrum of our patients is not limited to seizures but many of them show associated neurologic dysfunctions such as muscle tone alterations, irritability, and psychomotor retardation. The mutational spectrum of the present patients included 12 mutations, five already reported (c.500A<\/jats:styled-content>>G<\/jats:styled-content>, c.919C<\/jats:styled-content>>T<\/jats:styled-content>, c.1429G<\/jats:styled-content>>C<\/jats:styled-content>c.1217_1218delAT<\/jats:styled-content>, and c.1482\u20101G<\/jats:styled-content>>T<\/jats:styled-content>) and seven novel sequence changes (c.75C<\/jats:styled-content>>T<\/jats:styled-content>, c.319G<\/jats:styled-content>>T<\/jats:styled-content>, c.554_555delAA<\/jats:styled-content>, c.757C<\/jats:styled-content>>T<\/jats:styled-content>, c.787\u00a0+\u00a01G<\/jats:styled-content>>T<\/jats:styled-content>, c.1474T<\/jats:styled-content>>C<\/jats:styled-content>, c.1093\u2010?_1620+?). Only one mutation, p.G<\/jats:styled-content>477R<\/jats:styled-content>(c.1429G<\/jats:styled-content>>C<\/jats:styled-content>), was recurrent; this was detected in four different alleles. Transcriptional profile analysis of one patient's lymphoblasts and ex vivo splicing analysis showed the silent nucleotide change c.75C<\/jats:styled-content>>T<\/jats:styled-content>to be a novel splicing mutation creating a new donor splice site inside exon 1. Antisense therapy of the aberrantmRNA<\/jats:styled-content>splicing in a lymphoblast cell line harboring mutation c.75C<\/jats:styled-content>>T<\/jats:styled-content>was successful.<\/jats:p><\/jats:sec>Significance<\/jats:title>The present results broaden our knowledge ofPDE<\/jats:styled-content>, provide information regarding the genetic background ofPDE<\/jats:styled-content>inS<\/jats:styled-content>pain, afford data of use when making molecular\u2010based prenatal diagnosis, and provide a cellular proof\u2010of concept for antisense therapy application.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12083","type":"journal-article","created":{"date-parts":[[2013,1,25]],"date-time":"2013-01-25T14:18:49Z","timestamp":1359123529000},"page":"239-248","source":"Crossref","is-referenced-by-count":39,"title":["Clinical, biochemical, and molecular studies in pyridoxine\u2010dependent epilepsy. Antisense therapy as possible new therapeutic option"],"prefix":"10.1111","volume":"54","author":[{"given":"Bel\u00e9n","family":"P\u00e9rez","sequence":"first","affiliation":[{"name":"Center of Diagnosis of Molecular Diseases Center of Molecular Biology UAM\u2010CSIC Center for Biomedical Network Research on Rare Diseases (CIBERER) Institute for Health Research (IDIPAZ) Autonomous University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Gonz\u00e1lez","family":"Guti\u00e9rrez\u2010Solana","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hospital Ni\u00f1o Jes\u00fas Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Verd\u00fa","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hospital Virgen de la Salud Toledo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bego\u00f1a","family":"Merinero","sequence":"additional","affiliation":[{"name":"Center of Diagnosis of Molecular Diseases Center of Molecular Biology UAM\u2010CSIC Center for Biomedical Network Research on Rare Diseases (CIBERER) Institute for Health Research (IDIPAZ) Autonomous University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Yuste\u2010Checa","sequence":"additional","affiliation":[{"name":"Center of Diagnosis of Molecular Diseases Center of Molecular Biology UAM\u2010CSIC Center for Biomedical Network Research on Rare Diseases (CIBERER) Institute for Health Research (IDIPAZ) Autonomous University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Ruiz\u2010Sala","sequence":"additional","affiliation":[{"name":"Center of Diagnosis of Molecular Diseases Center of Molecular Biology UAM\u2010CSIC Center for Biomedical Network Research on Rare Diseases (CIBERER) Institute for Health Research (IDIPAZ) Autonomous University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocio","family":"Calvo","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hospital Carlos Haya M\u00e1laga Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil","family":"Jalan","sequence":"additional","affiliation":[{"name":"Department of NIRMAN Navi Mumbai Institute of Research (NIRMAN) Navi Mumbai India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura L\u00f3pez","family":"Mar\u00edn","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hospital Ni\u00f1o Jes\u00fas Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Campos","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Hospital Virgen de la Salud Toledo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria \u00c1ngeles","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Son Espases Palma de Mallorca Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta San","family":"Miguel","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hospital Montepr\u00edncipe Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hospital Gregorio Mara\u00f1\u00f3n Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margarita","family":"Castro","sequence":"additional","affiliation":[{"name":"Center of Diagnosis of Molecular Diseases Center of Molecular Biology UAM\u2010CSIC Center for Biomedical Network Research on Rare Diseases (CIBERER) Institute for Health Research (IDIPAZ) Autonomous University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Center of Diagnosis of Molecular Diseases Center of Molecular Biology UAM\u2010CSIC Center for Biomedical Network Research on Rare Diseases (CIBERER) Institute for Health Research (IDIPAZ) Autonomous University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Navarrete","sequence":"additional","affiliation":[{"name":"Center of Diagnosis of Molecular Diseases Center of Molecular Biology UAM\u2010CSIC Center for Biomedical Network Research on Rare Diseases (CIBERER) Institute for Health Research (IDIPAZ) Autonomous University of Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes Ruiz","family":"Desviat","sequence":"additional","affiliation":[{"name":"Center of Diagnosis of Molecular Diseases Center of Molecular Biology 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